The present invention relates to a series of new isoxazole derivatives, which are regarded as derivatives of isoxazolones, and which may be used for the treatment of cerebral circulatory problems and for use as centrally acting muscle relaxants. The invention also provides methods of using these compounds and processes for preparing them.
Cerebrovascular disorders, including stroke infarction, are among the main causes of death in the world today. Moreover, although the patient may survive in such cases, cognition impairment, which may be one of the sequelae of the disease, is a substantial social problem at present. For this reason, the development of therapeutic agents for the treatment of such disorders (commonly referred to as "cerebro-active drugs") is required.
Moreover, rigidity and/or spasticity are often observed as the sequelae of cerebrovascular disorders, such as cerebral stroke infarction, or as cerebrotraumatic sequelae, and make rehabilitation difficult. Centrally-acting muscle relaxants are available which can relieve such spasrigido hemiplegia, and act on the central nervous system. Examples of existing centrally-acting muscle relaxants include eperisone hydrochloride and afloqualone.
An object of the present invention is to provide new compounds which can be used as cerebro-active drugs and as centrally-acting muscle relaxants. Such compounds are needed which can treat cerebral circulatory problems and alleviate myotony and spasrigido hemiplegia, preferably without giving rise to accompanying drowsiness.
It is also a related object to provide a method of treating cerebrovascular disorders by the administration to a mammal, which may be human, suffering from or prone to cerebrovascular disorders of at least one cerebro-active drug.
Certain isoxazolone derivatives within the scope of formula (I) of the present invention are known which have the required effect. For example, Japanese Patent Application Kokai (i.e. as laid open to public inspection) Sho. No. 56-34674, discloses such compounds having anti-inflammatory, analgesic and anti-pyretic activities.
Additionally, certain compounds closely related to those of the present invention are disclosed in Japanese Patent Application Kokai Sho. No. 52-31070 (published March 1977) as discussed in detail below.